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BACKGROUND: Although a 1-year duration of dual antiplatelet therapy (DAPT) is used in many patients after drug-eluting stent (DES) implantation, the evidence supporting this duration is uncertain. OBJECTIVES: The authors investigated the risk-benefit profile of 1-year vs ≤6-month DAPT after DES using 2 novel scores to risk stratify bleeding and ischemic events. METHODS: Ischemic and bleeding risk scores were generated from ADAPT-DES (Assessment of Dual Antiplatelet Therapy with Drug-Eluting Stents), a multicenter, international, "all-comers" registry that enrolled 8,665 patients treated with DES. The risk-benefit profile of 1-year vs ≤6-month DAPT was then investigated across risk strata from an individual patient data pooled dataset of 7 randomized trials that enrolled 15,083 patients treated with DES. RESULTS: In the derivation cohort, the ischemic score and the bleeding score had c-indexes of 0.76 and 0.66, respectively, and both were well calibrated. In the pooled dataset, no significant difference was apparent in any ischemic endpoint between 1-year and ≤6-month DAPT, regardless of the risk strata. In the overall dataset, there was no significant difference in the risk of clinically relevant bleeding between 1-year and ≤6-month DAPT; however, among 2,508 patients at increased risk of bleeding, 1-year compared with ≤6-month DAPT was associated with greater bleeding (HR: 2.80; 95% CI: 1.12-7.13) without a reduced risk of ischemic events in any risk strata, including those with acute coronary syndromes. These results were consistent in a network meta-analysis. CONCLUSIONS: In the present large-scale study, compared with ≤6-month DAPT, a 1-year duration of DAPT was not associated with reduced adverse ischemic events in any risk strata (including acute coronary syndromes) but was associated with greater bleeding in patients at increased risk of bleeding.
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Síndrome Coronario Agudo , Stents Liberadores de Fármacos , Inhibidores de Agregación Plaquetaria , Factores de RiesgoRESUMEN
Background and objectives Whether prolonged dual antiplatelet therapy (DAPT) is more protective in patients with CKD and drug elutings tents compared with shorter DAPT isuncertain.The purposeofthismeta-analysis was to examine whether shorter DAPT in patients with drug-eluting stents and CKD is associated with lower mortality or major adverse cardiovascular event rates compared with longer DAPT. Design, setting, participants, & measurements A Medline literature research was conducted to identify randomized trials in patients with drug-eluting stents comparing different DAPT duration strategies.Inclusionof patients with CKD was alsorequired. The primary outcome was acomposite of all-cause mortality, myocardial infarction,stroke,orstent thrombosis (deï¬niteorprobable).Major bleeding was the secondary outcome.Therisk ratio (RR) was estimated using a random-effects model. Results Five randomized trials were included (1902 patient swith CKD).Short DAPT (#6months) was associated with a similar incidence of the primary outcome, compared with 12-month DAPT among patients with CKD (48 versus 50 events; RR, 0.93; 95% conï¬dence interval [95% CI], 0.64 to 1.36; P=0.72). Twelve-month DAPT was also associated with a similar incidence of the primary outcome compared with extended DAPT ($30 months) in the CKD subgroup (35 versus 35 events; RR, 1.04; 95% CI, 0.67 to 1.62; P=0.87). Numerically lower major bleeding eventrates were detected with shorter versus 12-monthDAPT(9versus13events;RR,0.69;95%CI,0.30 to1.60;P=0.39)and12-month versus extended DAPT( 9 versus 12 events;RR,0.83;95%CI,0.35to1.93;P=0.66)in patients with CKD.Conclusions Short DAPT does not appear to be inferior to longer DAPT in patients with CKD and drug-eluting stents.Because of imprecisioninestimates (feweventsandwide conï¬dence intervals),nodeï¬nite conclusion scan be drawn with respect to stent thrombosis. (AU)
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Humanos , Trastorno Mineral y Óseo Asociado a la Enfermedad Renal Crónica , Inhibidores de Agregación Plaquetaria , Stents Liberadores de FármacosRESUMEN
BACKGROUND: Prolonged dual anti-platelet therapy (DAPT) is intended to reduce ischemic events, at the cost of an increased bleeding risk in patients undergoing percutaneous coronary intervention (PCI). In this study, we evaluated whether race influences the ischemia/bleeding risk trade-off. METHODS: We searched for randomized clinical trials (RCTs) comparing DAPT duration after PCI. To compare the benefit or harm between DAPT duration by race, individual patient-level landmark meta-analysis was performed after discontinuation of the shorter duration DAPT group in each RCT. The primary ischemic endpoint was major adverse cardiac events (MACEs), and the primary bleeding endpoint was major bleeding events (clinicaltrials.gov NCT03338335). RESULTS: Seven RCTs including 16,518 patients (8,605 East Asians, 7,913 non-East Asians) were pooled. MACE occurred more frequently in non-East Asians (0.8% vs. 1.8%, p < 0.001), while major bleeding events occurred more frequently in East Asians (0.6% vs. 0.3%, p = 0.001). In Cox proportional hazards model, prolonged DAPT significantly increased the risk of major bleeding in East Asians (hazard ratio [HR], 2.843, 95% confidence interval [CI], 1.474-5.152, p = 0.002), but not in non-East Asians (HR, 1.375, 95% CI, 0.523-3.616, p = 0.523). East Asians had a higher median probability risk ratio of bleeding to ischemia (0.66 vs. 0.15), and the proportion of patients with higher probability of bleeding than ischemia was significantly higher in East Asians (32.3% vs. 0.4%, p < 0.001). CONCLUSION: We suggest that the ischemia/bleeding trade-off may be different between East Asians and non-East Asians. In East Asians, prolonged DAPT may have no effect in reducing the ischemic risk, while significantly increases the bleeding risk. (AU)
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Humanos , Inhibidores de Agregación Plaquetaria/uso terapéutico , Factores RacialesRESUMEN
OBJECTIVES: This study sought to evaluate the optimal duration of dual antiplatelet therapy (DAPT) after the implantation of a drug-eluting stent (DES) in elderly patients. BACKGROUND Qualified studies to evaluate the optimal duration of DAPT in elderly patients have been very limited. METHODS: Using 6 randomized trials that compared short-term (#6 months) and long-term (12 months) DAPT, individual participant data meta-analysis was performed in elderly patients ($65 years of age). The primary study outcome was the 12-month risk of a composite of myocardial infarction, definite or probable stent thrombosis, or stroke. The major secondary outcome was the 12-month risk of major bleeding. RESULTS: The primary outcome risk did not significantly differ between patients receiving short-term and long-term DAPT (hazard ratio [HR]: 1.12; 95% confidence interval [CI]: 0.88 to 1.43; p»0.3581) in the overall group of study participants. In subgroup analysis, a significant interaction between age and DAPT duration was observed for primary outcome risk (p for interaction»0.0384). In the subset of younger patients (<65 years of age, n»6,152), short-term DAPT was associated with higher risk of primary outcome (HR: 1.67; 95% CI: 1.14 to 2.44; p»0.0082). In elderly patients(n»5,319), however, the risk of primary outcome did not significantly differ between patients receiving short-term and long-term DAPT (HR: 0.84; 95% CI: 0.60 to 1.16; p»0.2856). Short-term DAPT was associated with a significant reduction in major bleeding compared with long-term DAPT (HR: 0.50; 95% CI: 0.30 to 0.84; p»0.0081) in the overall group, and particularly in elderly patients (HR: 0.46; 95% CI: 0.24-0.88; p»0.0196). CONCLUSIONS: Short-term DAPT after new-generation DES implantation may be more beneficial in elderly patients than in younger patients.
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Inhibidores de Agregación Plaquetaria , Accidente Cerebrovascular , Stents Liberadores de Fármacos , Infarto del MiocardioRESUMEN
OBJECTIVES: The study sought to evaluate the presence of a clinically relevant rebound phenomenon after dual antiplatelet therapy (DAPT) discontinuation in randomized trials. BACKGROUND: It is currently unknown whether clopidogrel discontinuation after short-term DAPT is associated with an early hazard of ischemic events. METHODS: The authors performed an individual participant data analysis and aggregate meta-analysis. The primary outcome was major adverse cardiac and cerebrovascular events (MACCE), defined as the composite of cardiac death, myocardial infarction (MI), or stroke. RESULTS: The study included 11,473 PCI patients with individual participant data from 6 randomized trials comparing short-term DAPT (3 or 6 months) versus long-term DAPT (12 months or more). During the first 90 days following clopidogrel discontinuation, there was no significant increase in the risk of MACCE between patients randomized to short-term DAPT compared with long-term DAPT (hazard ratio [HR]: 1.18; 95% confidence interval [CI]: 0.71 to 1.98; p»0.52; absolute risk difference 0.10%; 95% CI: 0.16% to 0.36%). The risk of MI or stent thrombosis was similar among patients randomized to short-term DAPT versus long-term DAPT (HR: 0.93; 95% CI: 0.46 to 1.90; p»0.85). In the aggregate data meta-analysis of 11 trials including 38,919 patients, a higher risk of early MACCE was observed after long-term ($12 months) DAPT duration (HR: 2.28; 95% CI: 1.69 to 3.09; p<0.001) but not short-term (<12 months) DAPT duration (HR: 1.08; 95% CI: 0.67 to 1.74; p for interaction»0.036).CONCLUSIONS: Among patients undergoing PCI with predominantly new-generation DES, discontinuation of clopidogrel after 3 or 6 months DAPT duration was not associated with an early increase in adverse clinical events. An early increase in MACCE was observed after long-term ($12 months) DAPT exposure.
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Humanos , Masculino , Femenino , Persona de Mediana Edad , Anciano , Intervención Coronaria Percutánea/efectos adversos , Intervención Coronaria Percutánea/instrumentación , Intervención Coronaria Percutánea/mortalidad , Reestenosis Coronaria/etnología , Trombosis Coronaria/etiologíaRESUMEN
AIM: We sought to determine whether the optimal dual antiplatelet therapy (DAPT) duration after drug-eluting stent (DES) placement varies according to clinical presentation.METHODS AND RESULTS:We performed an individual patient data pairwise and network meta-analysis comparing short-term (≤6-months) versus long-term (1-year) DAPT as well as 3-month vs. 6-month vs 1-year DAPT. The primary study outcome was the 1-year composite risk of myocardial infarction (MI) or definite/probable stent thrombosis (ST). Six trials were included in which DAPT after DES consisted of aspirin and clopidogrel. Among 11 473 randomized patients 6714 (58.5%) had stable CAD and 4758 (41.5%) presented with acute coronary syndrome (ACS), the majority of whom (67.0%) had unstable angina. In ACS patients, ≤6-month DAPT was associated with non-significantly higher 1-year rates of MI or ST compared with 1-year DAPT (Hazard Ratio (HR) 1.48, 95% Confidence interval (CI) 0.98-2.22; P = 0.059), whereas in stable patients rates of MI and ST were similar between the two DAPT strategies (HR 0.93, 95%CI 0.65-1.35; P = 0.71; Pinteraction = 0.09). By network meta-analysis, 3-month DAPT, but not 6-month DAPT, was associated with higher rates of MI or ST in ACS, whereas no significant differences were apparent in stable patients. Short DAPT was associated with lower rates of major bleeding compared with 1-year DAPT, irrespective of clinical presentation. All-cause mortality was not significantly different with short vs. long DAPT in both patients with stable CAD and ACS.
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Humanos , Masculino , Femenino , Persona de Mediana Edad , Hemorragia/inducido químicamente , Infarto del Miocardio , Muerte Súbita/epidemiologíaRESUMEN
BACKGROUND:Although some randomized controlled trials (RCTs) and meta-analyses have suggested that prolonged dual-antiplatelet therapy (DAPT) may be associated with increased mortality, the mechanistic underpinnings of this association remain unclear.OBJECTIVES:The aim of this study was to analyze the associations among bleeding, mortality, and DAPT duration after drug-eluting stent implantation in a meta-analysis of RCTs.METHODS:RCTs comparing different DAPT durations after drug-eluting stent placement were sought through the MEDLINE, Embase, and Cochrane databases and the proceedings of international meetings. Deaths were considered possibly bleeding related if occurring within 1 year of the episodes of bleeding. Primary analysis was by intention-to-treat. Secondary analysis was performed in a modified intention-to-treat population in which events occurring when all patients were on DAPT were excluded.
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Humanos , Hemorragia/inducido químicamente , Hemorragia/mortalidad , Inhibidores de Agregación Plaquetaria/administración & dosificación , Inhibidores de Agregación Plaquetaria/efectos adversos , Stents Liberadores de FármacosRESUMEN
BACKGROUND: Optimal upfront dual antiplatelet therapy (DAPT) duration after complex percutaneous coronary intervention (PCI) with drug-eluting stents (DES) remains unclear. OBJECTIVES: This study investigated the efficacy and safety of long-term (≥12 months) versus short-term (3 or 6 months) DAPT with aspirin and clopidogrel according to PCI complexity. METHODS: The authors pooled patient-level data from 6 randomized controlled trials investigating DAPT durations after PCI. Complex PCI was defined as having at least 1 of the following features: 3 vessels treated, ≥3 stents implanted, ≥3 lesions treated, bifurcation with 2 stents implanted, total stent length >60 mm, or chronic total occlusion. The primary efficacy endpoint was major adverse cardiac events (MACE), defined as the composite of cardiac death, myocardial infarction, or stent thrombosis. The primary safety endpoint was major bleeding. Intention-to-treat was the primary analytic approach. RESULTS: Of 9,577 patients included in the pooled dataset for whom procedural variables were available, 1,680 (17.5%) underwent complex PCI. Overall, 85% of patients received new-generation DES. At a median follow-up time of 392 days (interquartile range: 366 to 710 days), patients who underwent complex PCI had a higher risk of MACE (adjusted hazard ratio [HR]: 1.98; 95% confidence interval [CI]: 1.50 to 2.60; p < 0.0001)...
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Hemorragia , Infarto del Miocardio , Stents Liberadores de Fármacos , TrombosisRESUMEN
OBJECTIVE: To compare clinical outcomes between short term (up to 6 months) and long term (12 months) dual antiplatelet therapy (DAPT) after placement of a drug eluting stent in patients with and without diabetes.DESIGN: Individual participant data meta-analysis. Cox proportional regression models stratified by trial were used to assess the impact of diabetes on outcomes.DATA SOURCE: Medline, Embase, and Cochrane databases and proceedings of international meetings searched for randomised controlled trials comparing durations of DAPT after placement of a drug eluting stent. Individual patient data pooled from six DAPT trials.PRIMARY OUTCOME: Primary study outcome was one year risk of major adverse cardiac events (MACE), defined as cardiac death, myocardial infarction, or definite/probable stent thrombosis. All analyses were conducted by intention to treat...
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Diabetes Mellitus , StentsRESUMEN
Background: Whether the efficacy and safety of dual antiplatelet therapy (DAPT) are uniform between sexes is unclear. We sought to compare clinical outcomes between short-(6 months) versus long-term (1 year) DAPT after drug-eluting stent (DES) placement inwomen and men. Methods and Results: We pooled individual patient data from 6 randomizedtrials of DAPT (EXCELLENT, OPTIMIZE, PRODIGY, RESET, SECURITY, ITALIC PLUS).The primary outcome was 1-year risk of major adverse cardiac events (MACE). The mainsecondary outcome was 1-year risk of any bleeding. Out of the 11,473 randomized patients included in the pooled dataset, 3,454 (30%) were females. At 1-year follow-up, women hadhigher risk of MACE (3.6% vs. 2.8%; P 5 0.01) but similar risk of bleeding (1.9% vs. 1.6%;P 5 0.16) as compared with men. Compared with long-term DAPT, short-term DAPT wasassociated with similar rates of MACE in both women (HR 0.88; 95% CI 0.621.25) and men(HR 1.25; 95% CI 0.951.6; P interaction 5 0.08)]. At 1-year follow-up, short-term DAPT wasassociated with lower rates of bleeding as compared with long-term DAPT in both women(HR 0.84; 95% CI 0.511.37) and men (HR 0.58; 95% CI 0.400.84; Pinteraction 5 0.25). The presence of MVD was associated with higher MACE rates in the short-term DAPT group inwomen (HR: 1.16; CI 0.602.23) and men (HR: 2.29; CI 1.224.29; P interaction 5 0.25). Conclusions: Short-term DAPT is associated with similar rates of MACE but lower risk ofbleeding when as compared with prolonged DAPT. There was no significant difference between sexes in the population studied...